This is a first resubmission of the MESA Family Study, HL071205. The overall goals of the proposed MESA Family Study are to locate and identify genes contributing to sub-clinical cardiovascular disease (CVD), assessed by coronary calcium (CAC) and carotid intimal medial wall thickness (IMT) in U.S. minority populations. These goals will be addressed in a study of 2700 individuals from 900 sibships (sibtrios or larger), evenly distributed among African-Americans and Hispanic Americans, utilizing the existing framework of the NHLBI Multi-Ethnic Study of Atherosclerosis (MESA). In Aim 1, the MESA Family Study will determine the extent of genetic contribution to variation in CAC (EBCT and helical-gated CT scan) and IMT (B-mode ultrasound) in these two populations. This aim will be accomplished by examination (phenotyping) of 1800 siblings from 900 MESA index cases (evenly divided between African-Americans and Hispanic-Americans). In Aim 2, biological candidate regions in the human genome linked to these quantitative sub-clinical cardiovascular disease traits (coronary calcium and IMT) will be identified by genome scan approaches, including fine mapping of the best regions. This aim will use the MESA Study resources (Data Coordination Center, Central Laboratory, CT and Ultrasound Reading Center, 6 Clinical Field Centers) and the combined resources and cardiovascular genetic epidemiology expertise at Cedars-Sinai Medical Center and Wake-Forest School of Medicine. In Aim 3, gene localization and identification will be accomplished by association studies of positional as well as biological candidate genes in the subjects from the 3 minority populations of MESA (African-Americans, Hispanic-Americans, and Chinese-Americans). Whereas the purpose of MESA (the parent study) is to assess sub-clinical CVD and identify epidemiological risk factors in multi-ethnic populations, the purpose of the MESA Family Study is to identify the genes (quantitative trait loci, or QTLs) that contribute to these sub-clinical CVD risk factors. In combination with traditional risk factor assessment, identified inherited markers should be useful in the management of patients with vascular disease. These results will permit targeted diagnostic testing and pharmacologic intervention, and in the identification of subjects who could benefit from specific prevention protocols thus result in an increase in the overall well being of the US population.